Inflow Tract Development.

The development of the inflow tract is undoubtedly one of the most complex remodeling events in the formation of the four-chambered heart. It involves the creation of two separate atrial chambers, the formation of an atrial/atrioventricular (AV) septal complex, the incorporation of the caval veins and coronary sinus into the right atrium, and the remodeling events that result in pulmonary venous return draining into the left atrium. In these processes, the atrioventricular mesenchymal complex, consisting of the major atrioventricular (AV) cushions, the mesenchymal cap on the primary atrial septum (pAS), and the dorsal mesenchymal protrusion (DMP), plays a crucial role.

Coronary Sinus Ablation Is a Key Player Substrate in Recurrence of Persistent Atrial Fibrillation.

Atrial fibrillation (AF) is the most frequent atrial arrhythmia. During the last few decades, owing to numerous advancements in the field of electrophysiology, we reached satisfactory outcomes for paroxysmal AF with the help of ablation procedures. But the most challenging type is still persistent AF. The recurrence rate of AF in patients with persistent AF is very high, which shows the inadequacy of pulmonary vein isolation (PVI). Over the last few decades, we have been trying to gain insight into AF mechanisms, and have come to the conclusion that there must be some triggers and substrates other than pulmonary veins. According to many studies, PVI alone is not enough to deal with persistent AF. The purpose of our review is to summarize updates and to clarify the role of coronary sinus (CS) in AF induction and propagation. This review will provide updated knowledge on developmental, histological, and macroscopic anatomical aspects of CS with its role as arrhythmogenic substrate. This review will also inform readers about application of CS in other electrophysiological procedures.

Drainage of the Left Hepatic Vein into the Coronary Sinus, a Rare Intraoperative Finding.

In a 76-year-old female undergoing coronary artery bypass surgery, a persistent left hepatic vein was observed. Draining of this vein into the coronary sinus is an extremely rare embryological malformation and this is the first case to be reported as a solitary malformation in absence of other cardiac malformations.

Asymmetric fate of the posterior part of the second heart field results in unexpected left/right contributions to both poles of the heart.

RATIONALE: The second heart field (SHF) contains progenitors of all heart chambers, excluding the left ventricle. The SHF is patterned, and the anterior region is known to be destined to form the outflow tract and right ventricle. OBJECTIVE: The aim of this study was to map the fate of the posterior SHF (pSHF). METHODS AND RESULTS: We examined the contribution of pSHF cells, labeled by lipophilic dye at the 4- to 6-somite stage, to regions of the heart at 20 to 25 somites, using mouse embryo culture. Cells more cranial in the pSHF contribute to the atrioventricular canal (AVC) and atria, whereas those more caudal generate the sinus venosus, but there is intermixing of fate throughout the pSHF. Caudal pSHF contributes symmetrically to the sinus venosus, but the fate of cranial pSHF is left/right asymmetrical. Left pSHF moves to dorsal left atrium and superior AVC, whereas right pSHF contributes to right atrium, ventral left atrium, and inferior AVC. Retrospective clonal analysis shows the relationships between AVC and atria to be clonal and that right and left progenitors diverge before first and second heart lineage separation. Cranial pSHF cells also contribute to the outflow tract: proximal and distal at 4 somites, and distal only at 6 somites. All outflow tract-destined cells are intermingled with those that will contribute to inflow and AVC. CONCLUSIONS: These observations show asymmetric fate of the pSHF, resulting in unexpected left/right contributions to both poles of the heart and can be integrated into a model of the morphogenetic movement of cells during cardiac looping.

Wt1 and retinoic acid signaling in the subcoelomic mesenchyme control the development of the pleuropericardial membranes and the sinus horns.

RATIONALE: The cardiac venous pole is a common focus of congenital malformations and atrial arrhythmias, yet little is known about the cellular and molecular mechanisms that regulate its development. The systemic venous return myocardium (sinus node and sinus horns) forms only late in cardiogenesis from a pool of pericardial mesenchymal precursor cells. OBJECTIVE: To analyze the cellular and molecular mechanisms directing the formation of the fetal sinus horns. METHODS AND RESULTS: We analyzed embryos deficient for the Wt1 (Wilms tumor 1) gene and observed a failure to form myocardialized sinus horns. Instead, the cardinal veins become embedded laterally in the pleuropericardial membranes that remain tethered to the lateral body wall by the persisting subcoelomic mesenchyme, a finding that correlates with decreased apoptosis in this region. We show by expression analysis and lineage tracing studies that Wt1 is expressed in the subcoelomic mesenchyme surrounding the cardinal veins, but that this Wt1-positive mesenchyme does not contribute cells to the sinus horn myocardium. Expression of the Raldh2 (aldehyde dehydrogenase family 1, subfamily A2) gene was lost from this mesenchyme in Wt1(-/-) embryos. Phenotypic analysis of Raldh2 mutant mice rescued from early cardiac defects by retinoic acid food supply revealed defects of the venous pole and pericardium highly similar to those of Wt1(-/-) mice. CONCLUSIONS: Pericardium and sinus horn formation are coupled and depend on the expansion and correct temporal release of pleuropericardial membranes from the underlying subcoelomic mesenchyme. Wt1 and downstream Raldh2/retinoic acid signaling are crucial regulators of this process. Thus, our results provide novel insight into the genetic and cellular pathways regulating the posterior extension of the mammalian heart and the formation of its coelomic lining.

Z-scores of early diastolic blood flow widths of mitral and tricuspid valves in normal fetuses and fetuses with dilated coronary sinus.

Objectives: To establish Z-score models for early diastolic blood flow widths of mitral and tricuspid valves in normal fetuses and compare Z-scores and other blood flow dynamic parameters between normal fetuses and fetuses with dilated coronary sinus (CS). This study seeks to assess whether dilated CS affects cardiac structure or hemodynamics.Methods: One hundred twenty-nine normal fetuses (Group I) and 15 fetuses with dilated CS connected to persistent left superior vena cava (PLSVC) (Group II) were included in this study. Noncardiac biometrical parameters, including gestation age (GA), biparietal diameter (BPD), femoral length (FL), and heart area (HA), were obtained. Hemodynamic parameters, such as the early diastolic blood flow widths of mitral and tricuspid valves (MV-CDFI-Width, TV-CDFI-Width), velocity and time integral of blood flow (VTI), peak early and late diastolic velocity of mitral and tricuspid valves [peak early diastolic velocity of the mitral valve (MVE), peak late diastolic velocity of the mitral valve (MVA), peak early diastolic velocity of the tricuspid valve (TVE), peak late diastolic velocity of the tricuspid valve (TVA)], were measured.Results: Z-score models for MV-CDFI-Width and TV-CDFI-Width against noncardiac biometrical parameters were best described by linear regression analysis. The mean equations of MV-CDFI-Width against noncardiac biometrical parameters were 0.066 + (0.025 × GA), 0.169 + (0.084 × BPD), 0.213 + (0.106 × FL) and 0.533 + (0.028 × HA). The SD for MV-CDFI-Width against FL was estimated based on values from the following equation: -0.006 + (0.02 × FL). Other SDs were constants estimated as the standard deviations of the unscaled residuals. Z-scores and other blood flow dynamic parameters exhibited no statistically significant differences between Group I and Group II.Conclusions: This study demonstrated that dilated CS did not affect fetal hemodynamics of the mitral or tricuspid valves or cardiac structures. We also suggested that the causes of diminutive left heart or coarctation of the aorta might not be associated with dilated CS in fetuses with PLSVC.

Control of sinus venous valve and sinoatrial node development by endocardial NOTCH1.

AIMS: Sinus venous valve (SVV) and sinoatrial node (SAN) develop together at the sinoatrial junction during embryogenesis. SVV ensures unidirectional cardiac input and SAN generates sinus rhythmic contraction, respectively; both functions are essential for embryonic survival. We aim to reveal the potential role of endocardial NOTCH signalling in SVV and SAN formation. METHODS AND RESULTS: We specifically deleted Notch1 in the endocardium using an Nfatc1Cre line. This deletion resulted in underdeveloped SVV and SAN, associated with reduced expression of T-box transcription factors, Tbx5 andTbx18, which are essential for the formation of SVV and SAN. The deletion also led to decreased expression of Wnt2 in myocardium of SVV and SAN. WNT2 treatment was able to rescue the growth defect of SVV and SAN resulted from the Notch1 deletion in whole embryo cultures. Furthermore, the Notch1 deletion reduced the expression of Nrg1 in the SVV myocardium and supplement of NRG1 restored the growth of SVV in cultured Notch1 knockout embryos. CONCLUSION: Our findings support that endocardial NOTCH1 controls the development of SVV and SAN by coordinating myocardial WNT and NRG1 signalling functions.

Comparison of coronary sinus diameter Z-scores in normal fetuses and fetuses with persistent left superior vena cava (PLSVC).

To establish Z-score reference ranges for coronary sinus (CS) diameter in normal fetuses and explore the diagnostic value of CS Z-score in fetuses with persistent left superior vena cava (PLSVC). Study of 235 normal fetuses and 30 fetuses with PLSVC was involved. Noncardiac biometrical parameters included biparietal diameter (BPD), femoral length (FL), heart area (HA), gestation age (GA). The coronary sinus systolic and diastolic diameter (CSDs and CSDd ) were measured at the end of systole and diastole. CSDs and CSDd Z-score models were constructed by using linear regression analysis with Non-cardiac biometrical parameters as independent variables. Z-scores between normal fetuses and fetuses with PLSVC were compared. A simple, linear regression model was the best description and correlations between fetal CSDs and CSDd and four independent variables were excellent. Reference ranges for predicting means and SDs of the fetal CS were established. Equations for Z-score calculation were provided, CSDs and CSDd Z-scores were statistically different between normal fetuses and those with PLSVC. Development of CSDs and CSDd Z-score reference ranges in normal fetuses was realized. The CSDs and CSDd Z-scores can provide quantitative evidence in prenatal diagnosis of PLSVC.

Morphometry of the triangle of Koch and position of the coronary sinus opening in cadaveric fetal hearts.

AIMS: The aim of the present study was to determine the variations in the position of the coronary sinus (CS) ostium in normal cadaveric fetal (28 weeks or more) hearts and to assess the impact that these variations had on the dimensions of the triangle of Koch (TK). METHODS: This cross-sectional analytical study was conducted on 28 fetal hearts. The dimensions and area of the TK were calculated by two methods, M1 (anatomical) and M2 (clinical). The position of the CS was defined with respect to the tendon of Todaro. Differences between M1 and M2 were estimated using the paired T test. Pearson's correlation coefficient and the adjusted correlation coefficient were used to estimate the strength of association between measurements made by the methods. RESULTS: Ten (35.7%) cadavers were male and 18 (64.3%) female. The mean gestational age was 32.4±3.3 weeks. Using M1, the mean dimensions of the triangle in millimeters (mm) were 9.2±2.2, 6.6±1.8, and 6±2.4 respectively for a, b and c. Similarly, the dimensions using M2 were 7±2.1, 4.7±1.5, and 4.8±2.2. The area in mm2 was 20.4±10.4 and 11.7±6.7 using M1 and M2 respectively. All measurements were significantly greater with M1. All correlation coefficients were high and significant. The CS ostium and tendon of Todaro maintained a relatively constant positional relationship. CONCLUSIONS: Significantly higher values were noted in the dimensions of TK using M1. High significant positive correlations were observed in measurements made by the two methods. The CS ostium was relatively constantly placed within the TK.